Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19
Authors: Susanna Naggie, David R. Boulware, Christopher J. Lindsell, Thomas G. Stewart, Nina Gentile, Sean Collins, Matthew William McCarthy, Dushyantha Jayaweera, Mario Castro, Mark Sulkowski, Kathleen McTigue, Florence Thicklin, G. Michael Felker, Adit A. Ginde, Carolyn T. Bramante, Alex J. Slandzicki, Ahab Gabriel, Nirav S. Shah, Leslie A. Lenert, Sarah E. Dunsmore, Stacey J. Adam, Allison DeLong, George Hanna, April Remaly, Rhonda Wilder, Sybil Wilson, Elizabeth Shenkman, Adrian F. Hernandez, William (Kelly) Vincent, Raina Vincent, Ray Bianchi, Jen Premas, Diana Cordero-Loperena, Evelyn Rivera, Madhu Gupta, Greg Karawan, Carey Ziomek, Joseph Arena, Sonaly DeAlmeida, Soroush Ramin, Jaya Nataraj, Michael Paasche-Orlow, Lori Henault, Katie Waite, David Miller, Ginger Brounce, Constance George-Adebayo, Adeolu Adebayo, Jessica Wallan, Alex Slandzicki, Claudia Vogel, Sebastian Munoz, David Kavtaradze, Cassandra Watson, David Singleton, Maria Rivon, Amanda Sevier, Arnold Del Pilar, Amber Spangler, Sohail Rao, Luis Cantu, Arvind Krishna, Kathy Evans, Tylene Falkner, Brandi Kerr, Robert Spees, Mailyn Marta, G. Michael Felker, Amanda Harrington, Rowena Dolor, Madison Frazier, Lorraine Vergara, Jessica Wilson, Valencia Burruss, Terri Hurst, Igho Ofotokun, Laurel Bristow, Rajesh Prabhu, Krystal Klicka, Amber Lightfeather, Vicki James, Marcella Rogers, Pradeep Parihar, De'Ambra Torress, Chukwuemeka Oragwu, Ngozi Oguego, Rajesh Pillai, Mustafa Juma, Ahab Gabriel, Emad Ghaly, Dafer Al-Haddadin, Courtney Ramirez, Gammal Hassanien, Samah Ismail, Andrew Meltzer, Seamus Moran, Scott Brehaut, Angelina Roche, Manisha Mehta, Nicole Koppinger, Jose Baez, Ivone Pagan, Dallal Abdelsayed, Mina Aziz, Philip Robinson, Julie Nguyen, Victoria Pardue, Llisa Hammons, Juan Ruiz-Unger, Susan Gonzalez, Lionel Reyes, John Cienki, Gisselle Jimenez, Jonathan Cohen, Matthew Wong, Ying Yuan, Jeremy Szeto, Mark Sulkowski, Lauren Stelmash, Arch Amon, Daniel Haight, Deryl Lamb, Amron Harper, Nancy Pyram-Bernard, Arlen Quintero, Eftim Adhami, Josette Maria, Diksha Paudel, Oksana Raymond, Jeffrey Summers, Tammy Turner, Leslie Lenert, Sam Gallegos, Elizabeth Ann Szwast, Ahsan Abdulghani, Pravin Vasoya, Conrad Miller, Hawa Wiley, Nirav Shah, Tovah Klein, Julie Castex, Phillip Feliciano, Jacqueline Olivo, Marian Ghaly, Zainub Javed, Alexandra Nawrocki, Anthony Vecchiarelli, Nikki Vigil, Vijaya Cherukuri, Erica Burden, Dawn Linn, Laura Fisher, Vijay Patel, Praksha Patel, Yuti Patel, Leonard Ellison, Jeffrey Harrison, Binod Shah, Sugata Shah, Upinder Singh, Julia Donahue, Yasmin Jazayeri, Anita Gupta, N Chandrasekar, Beth Moritz, Tabitha Fortt, Anisa Fortt, Ingrid Jones-Ince, Alix McKee, Christy Schattinger, Jason Wilson, Brenda Farlow, Nina Gentile, Lillian Finlaw, Randall Richwine, Tearani Williams, Penny Paizer, Lisa Carson, Edward Michelson, Danielle Austin, Sangeeta Khetpal, Tiffany Cantrell, Drew Franklin, Karissa Marshall, Arvind Mahadevan, Madelyn Rosequist, Martin Gnoni, Crystal Daffner, Carla VandeWeerd, Mitchell Roberts, Mark D'Andrea, Stephen Lim, Wayne Swink, Margaret Powers-Fletcher, Sylvere Mukunzi, Elizabeth Shenkman, Jamie Hensley, Brittney Manning, Carmen Isache, Jennifer Bowman, Angelique Callaghan-Brown, Taylor Scott, Tiffany Schwasinger-Schmidt, Ashlie Cornejo, Dushyantha Jayaweera, Maria Almanzar, Letty Ginsburg, Americo Hajaz, Carolyn Bramante, Matthew Robinson, Michelle Seithel, Akira Sekikawa, Emily Klawson, Luis Ostrosky, Virginia Umana, Thomas Patterson, Robin Tragus, Patrick Jackson, Caroline Hallowell, Heather Haughey, Bhavna Vaidya-Tank, Cameron Gould, Parul Goyal, Carly Gatewood, John Williamson, Hannah Seagle, Matthew McCarthy, Elizabeth Salsgiver, Eddie Armas, Jhonsai Cheng, Priscilla Huerta, Julia Garcia-Diaz, David Aamodt, JaMario Ayers, Jess Collins, John Graves, James Grindstaff, Frank Harrell, Jessica Lai, Itzel Lopez, Jessica Marlin, Alyssa Merkel, Sam Nwosu, Savannah Obregon, Dirk Orozco, Yoli Perez-Torres, Nelson Prato, Colleen Ratcliff, Max Rhode, Russell Rothman, Jana Shirey-Rice, Krista Vermillion, Hsi-Nien Tan, Seibert Tregoning, Meghan Vance, Amber Vongsamphanh, Maria Weir, Nicole Zaleski
Journal: JAMA (2022)

The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown.To evaluate the efficacy of ivermectin, 400 μg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19.ACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US.Participants were randomized to receive ivermectin, 400 μg/kg (n = 817), daily for 3 days or placebo (n = 774).Time to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28.Among 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]).Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19.ClinicalTrials.gov Identifier: NCT04885530.